Modulation of adrenal aldosterone release by oxidative modification of low-density lipoprotein.

Abstract

BACKGROUND:

Serum aldosterone is a causative factor for various metabolic and cardiovascular disorders. Low-density lipoprotein (LDL) is a major cholesterol source for aldosterone steroidogenesis; however, the effect of oxidative modification of LDL on aldosterone release is not known. We studied the effect of hypochlorite-oxidized LDL (oxLDL) on adrenal aldosterone secretion.

METHODS:

LDL (native LDL (natLDL)) was obtained from healthy volunteers and oxidatively modified in vitro. NCI-H295R cells were stimulated with natLDL and oxLDL, and the aldosterone release was quantified by radioimmunoassay. Molecular changes were studied with western blot analysis and quantitative RT-PCR analysis.

RESULTS:

NatLDL and oxLDL caused dose-dependent increase in aldosterone release up to threefold. However, the stimulatory effects of modified LDL on aldosterone secretion decreased with increasing degree of LDL oxidation. 24-h incubations with natLDL, mild- and medium-oxidized LDL sensitized the adrenocortical cells to subsequent angiotensin II (Ang II) stimulations by 2.9-, 2.8-, and 2.5-folds, respectively. Heavily oxidized LDL did not sensitize the cells to Ang II stimulations to a similar extent. At the molecular level, the ERK pathway was activated within a minute by both natLDL and oxLDL; however, oxLDL showed a stronger (2.75-fold at 1 and 15 min) and longer (15 min) activation of ERK than natLDL (twofold).

CONCLUSIONS:

This study demonstrates the following: (i) both natLDL and hypochlorite-oxidized LDL utilize ERK pathway to mediate aldosterone release; (ii) mildly oxidized LDL sensitizes the adrenocortical cells to further stimulations by Ang II similar to natLDL that may have a role in pathological processes; (iii) extensive LDL oxidation counteracts adrenocortical aldosterone release.

• Authors: Ishrath Ansurudeen, Jens Pietzsch, Juergen Graessler, Monika Ehrhart-Bornstein, Sarama Saha, Stefan R Bornstein, Steffi Kopprasch
• Journal: American journal of hypertension (Am J Hypertens) Vol. 23 Issue 10 Pg. 1061-8 (Oct 2010) ISSN: 1941-7225 [Electronic] United States
• PMID: 20559286 (Publication Type: Journal Article)

Chemical References

• Lipoproteins, LDL
• Oxidants
• Receptors, LDL
• Steroids
• Thiobarbituric Acid Reactive Substances
• oxidized low density lipoprotein
• Angiotensin II
• Aldosterone
• RNA
• Hypochlorous Acid
• Extracellular Signal-Regulated MAP Kinases

Topics

• Adrenal Cortex (drug effects, metabolism)
• Adrenal Glands (drug effects, metabolism)
• Aldosterone (metabolism)
• Angiotensin II (pharmacology)
• Blotting, Western
• Cell Line
• Dose-Response Relationship, Drug
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Hypochlorous Acid (chemistry)
• Lipoproteins, LDL (chemistry, pharmacology)
• Oxidants (chemistry)
• RNA (biosynthesis, isolation & purification)
• Receptors, LDL (drug effects, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Steroids (biosynthesis)
• Stimulation, Chemical
• Thiobarbituric Acid Reactive Substances (metabolism)